DNA sequencing using multiple metal layer structure with different organic coatings forming different transient bondings to DNA

ABSTRACT

A nanodevice includes a reservoir filled with conductive fluid and a membrane separating the reservoir. A nanopore is formed through the membrane having electrode layers separated by insulating layers. A certain electrode layer has a first type of organic coating and a pair of electrode layers has a second type. The first type of organic coating forms a motion control transient bond to a molecule in the nanopore for motion control, and the second type forms first and second transient bonds to different bonding sites of a base of the molecule. When a voltage is applied to the pair of electrode layers a tunneling current is generated by the base in the nanopore, and the tunneling current travels via the first and second transient bonds formed to be measured as a current signature for distinguishing the base. The motion control transient bond is stronger than first and second transient bonds.

DOMESTIC PRIORITY

This application is a divisional of U.S. patent application Ser. No.15/005,174 filed Jan. 10, 2016, which is a divisional of U.S. patentapplication Ser. No. 14/624,868 filed Feb. 18, 2015, which is adivisional application of U.S. patent application Ser. No. 13/359,766filed Jan. 27, 2012, which claims the benefit of U.S. Provisional PatentApplication 61/437,115 filed on Jan. 28, 2011, the contents of which areherein incorporated by reference in their entirety.

BACKGROUND

Exemplary embodiments relate to nanodevices, and more specifically to amultiple layer structure with one or more organic coatings.

Nanopore sequencing is a method for determining the order in whichnucleotides occur on a strand of deoxyribonucleic acid (DNA). A nanoporecan be a small hole in the order of several nanometers in internaldiameter. The theory behind nanopore sequencing is about what occurswhen the nanopore is immersed in a conducting fluid and an electricpotential (voltage) is applied across the nanopore. Under theseconditions, a slight electric current due to conduction of ions throughthe nanopore can be measured, and the amount of current is verysensitive to the size and shape of the nanopore. If single bases orstrands of DNA pass (or part of the DNA molecule passes) through thenanopore, this can create a change in the magnitude of the currentthrough the nanopore. Other electrical or optical sensors can also bepositioned around the nanopore so that DNA bases can be differentiatedwhile the DNA passes through the nanopore.

The DNA can be driven through the nanopore by using various methods. Forexample, an electric field might attract the DNA towards the nanopore,and it might eventually pass through the nanopore. The scale of thenanopore can have the effect that the DNA may be forced through the holeas a long string, one base at a time, like thread through the eye of aneedle.

BRIEF SUMMARY

According to an exemplary embodiment, a nanodevice is provided. Thenanodevice includes a reservoir filled with a conductive fluid, and amembrane separating the reservoir, where the membrane includes electrodelayers separated by insulating layers. A nanopore is formed through themembrane. A certain electrode layer has a first type of organic coatingand a pair of electrode layers has a second type of organic coatinginside the nanopore. The first type of organic coating on the certainelectrode layer forms a motion control transient bond to a molecule inthe nanopore for motion control of the molecule, and the second type oforganic coating on the pair of electrode layers forms first and secondtransient bonds to different bonding sites of a base of the molecule inthe nanopore. When a voltage is applied to the pair of electrode layersa tunneling current is generated by the base in the nanopore, and thetunneling current travels via the first and the second transient bondsformed to the base to be measured as a current signature fordistinguishing the base. The motion control transient bond is strongerthan the first and the second transient bonds.

According to an exemplary embodiment, a system is provided. The systemincludes a nanodevice. The nanodevice includes a reservoir filled with aconductive fluid, and a membrane separating the reservoir, where themembrane includes electrode layers separated by insulating layers. Ananopore is formed through the membrane. A certain electrode layer has afirst type of organic coating and a pair of electrode layers has asecond type of organic coating inside the nanopore. The first type oforganic coating on the certain electrode layer forms a motion controltransient bond to a molecule in the nanopore for motion control of themolecule, and the second type of organic coating on the pair ofelectrode layers forms first and second transient bonds to differentbonding sites of a base of the molecule in the nanopore. The systemincludes a voltage source configured to apply a voltage. When thevoltage is applied by the voltage source to the pair of electrode layersa tunneling current is generated by the base in the nanopore, and thetunneling current travels via the first and the second transient bondsformed to the base to be measured as a current signature fordistinguishing the base. The motion control transient bond is strongerthan the first and second transient bonds.

According to an exemplary embodiment, a nanodevice is provided. Thenanodevice includes a reservoir filled with a conductive fluid, and amembrane separating the reservoir, where the membrane includes electrodelayers separated by insulating layers. A nanopore is formed through themembrane. A certain electrode layer has a first type of organic coatingand a pair of electrode layers has a second type of organic coatinginside the nanopore. The first type of organic coating on the certainelectrode layer forms a motion control transient bond to a molecule inthe nanopore for motion control of the molecule. The second type oforganic coating on the pair of electrode layers forms a first transientbond to a first base and a second transient bond to a second base of themolecule in the nanopore. When a voltage is applied to the pair ofelectrode layers a tunneling current is generated though the first basealong the molecule to the second base in the nanopore. The tunnelingcurrent travels via the first and the second transient bondsrespectively to be measured as a current signature for distinguishingthe first base and the second base. The motion control transient bond isstronger than the first and the second transient bonds.

According to an exemplary embodiment, a nanodevice is provided. Thenanodevice includes a substrate, a nanochannel formed in the substrate,a first pair of electrodes having a nanometer size gap there between,and a second pair of electrodes having a nanometer size gap therebetween. The first and second pair of electrodes are positioned alongthe nanochannel and in the substrate. A first organic coating is on anexposed surface of the first pair of electrodes at an inner surface ofthe nanochannel. The first organic coating forms a first transient bondbetween the first pair of electrodes and a base of a molecule in thenanochannel. A second organic coating is on an exposed surface of thesecond pair of electrodes at an inner surface of the nanochannel. Thesecond organic coating forms a second transient bond between the secondpair of electrodes and another base of the molecule in the nanochannel.When a first voltage is applied to the first pair of electrodes, atunneling current is generated by the base in the nanochannel. Thetunneling current travels through the first transient bond formed to thebase to be measured as a current signature for distinguishing the base.

Other systems, methods, apparatus, design structures, and/or computerprogram products according to embodiments will be or become apparent toone with skill in the art upon review of the following drawings anddetailed description. It is intended that all such additional systems,methods, apparatus, design structures, and/or computer program productsbe included within this description, be within the scope of theexemplary embodiments, and be protected by the accompanying claims. Fora better understanding of the features, refer to the description and tothe drawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The subject matter which is regarded as the invention is particularlypointed out and distinctly claimed in the claims at the conclusion ofthe specification. The forgoing and other features are apparent from thefollowing detailed description taken in conjunction with theaccompanying drawings in which:

FIG. 1 illustrates a schematic of a nanopore device in accordance withan exemplary embodiment.

FIG. 2 illustrates a schematic of a nanopore device in accordance withan exemplary embodiment.

FIG. 3 illustrates a schematic of a nanopore device in accordance withan exemplary embodiment.

FIG. 4 illustrates molecules of the organic coating according to anexemplary embodiment.

FIG. 5 illustrates molecules of the organic coating according to anexemplary embodiment.

FIG. 6 illustrates a computer utilized according to exemplaryembodiments.

FIG. 7 illustrates a flow chart according to an exemplary embodiment.

FIG. 8 illustrates a flow chart according to an exemplary embodiment.

DETAILED DESCRIPTION

Exemplary embodiments provide an organic-coated nanopore through a stackof repetitive insulating/conducting/insulating/conducting/insulating/ .. . layers. Exemplary embodiments leverage the transient bonding betweenthe organic coating and the DNA bases to control the motion of the DNA,and then utilize the tunneling current through the DNA base fordifferentiating the DNA base while the DNA base is transiently bonded tothe organic coating.

Recently, there has been growing interest in applying nanopores assensors for rapid analysis of biomolecules such as deoxyribonucleic acid(DNA), ribonucleic acid (RNA), protein, etc. Special emphasis has beengiven to applications of nanopores for DNA sequencing, as thistechnology holds the promise to reduce the cost of sequencing below$1000/human genome. Two issues in nanopore DNA sequencing arecontrolling the translocation of DNA through the nanopore anddifferencing individual DNA bases.

As illustrated in an exemplary embodiment, the use of a nanopore througha stack of repetitiveinsulating/conducting/insulating/conducting/insulating/ . . . layers isproposed, and all conductive surfaces at the inner-surface of thenanopore are coated with an organic layer, which can transiently bond toindividual DNA bases. Thus, the DNA can be temporarily trapped insidethe nanopore when enough of these transient bonds are present. Thenegatively charged DNA can be controllably driven through the nanoporeby an external electrical field along the nanopore if one tunes theelectrical field to alternatively be above and below the threshold ofbreaking all transient bonds. All conducting layers are electricallyaddressed by respective voltage sources and the tunneling currentbetween adjacent conductive layers is measured while individual DNAbases are temporally bonded to them. Since DNA bases are temporarilyfixed during the measurements, the tunneling current will have enoughresolution to differentiate DNA bases. Note that multiple conductinglayers provide the necessary trapping energy (e.g., multiple bondinglocations) of DNA as well as redundant data of tunneling current forerror check. DNA can also be driven back and forth through the nanoporemany times by switching the polarity of the external electrical field ofthe voltage source, for repeated measurements.

According to an exemplary embodiment, multiple conducting layers aredifferentially coated so that some bonds will be optimized for motioncontrol and other bonds will be optimized for DNA base sensing. Themultiple conducting layers can also be made from two or more differentmaterials so that different organic coatings can be applied to eachmaterial of the conducting layers.

Now turning to FIG. 1, FIG. 1 illustrates a schematic 100 of anorganic-coated nanopore through a stack of repetitiveinsulating/conducting/insulating/conducting/insulating/ . . . layers forDNA motion control and base sensing, for the case that tunneling currentis measured through a single DNA base according to an exemplaryembodiment.

A membrane 10 is made of films 101, 102, 103, 104, 105, 106, and 107,and the membrane 10 partitions a reservoir 110 into two parts. FIG. 1 isa cross-sectional view of the reservoir 110. A nanometer size hole 108is made through the membrane 10. Membrane part 101, 103, 105, and 107are electrically insulating while membrane parts 102, 104, and 106 areelectrically conducting. Layers 101 and 107 are electrical passivationlayers, and layers 103 and 105 are insulating inter-layers betweenconductive layers. Only three conductive layers 102, 104, and 106 areshown in the FIG. 1, but exemplary embodiments are not limited to threeconductive layers. It is contemplated that two or more conductive layersmay be utilized. The conductive layers 102, 104, and 106 are electrodesand may also be referred to as electrodes herein.

Organic coating 109 is made on the surface of conductive layers 102 and104, while organic coating 122 is made on the surface of conductivelayer 106. Organic coating 109 and 122 can be any organic coating thathas transient bonding 117 and 123 respectively (such as, e.g., ahydrogen bond) with individual DNA bases 113 and/or DNA backbone 125(for organic coating 122). The DNA backbone 125 is the line between(i.e., connecting) DNA bases 113. The minimum number of conductivelayers is determined by the need for trapping DNA molecules 112 (i.e.,DNA) inside the nanopore against thermal agitation via the transientbonds 117 and 123. The reservoir 110 and the nanopore 108 are thenfilled with solvent 111 (e.g., a conducive solution). DNA molecules 112(in which bases are illustrated as 113 and the backbone is illustratedas 125) are loaded into the nanopore 108 by an electrical voltage biasof voltage source 116 (which produces an electric field), applied acrossthe nanopore 108 via two electrochemical electrodes 114 and 115, whichwere dipped in the solvent 111 of the two parts of reservoir 110.

With the desired number of conductive layers 102, 104, and 106 (thusproducing enough transient bonds 117 and 123), the DNA molecule 112 canbe trapped inside the nanopore 108 against thermal motion. With apredefined voltage of the voltage source 116, these transient bonds 117and 123 can be broken, and the DNA 112 can be driven through thenanopore 108 via the electrical field produced by the voltage source116. If the voltage source 116 is pulsed, the DNA 112 will (alternately)experience a bonded phase (fixed in position) and moving phase. At thebonded phase, voltages of voltage sources 118 and 119 can be appliedbetween adjacent conductive layers 102 and 104, and/or adjacentconductive layers 104 and 106 respectively. Accordingly, tunnelingcurrent 120 can be measured by its corresponding ammeter (A), andtunneling current 121 can be measured by its corresponding ammeter (A).Since the DNA base 113 is fixed during the bonding phase, thesetunneling current (signatures) 120 and 121 can be used to identifyindividual DNA bases 113. The moving phase (when the voltage source 116is applied) will advance the DNA 112 through the nanopore 108 foridentifying other DNA bases 113. The DNA 112 can also be driven back andforth through the nanopore 108 many times by switching the polarity ofthe external voltage bias of voltage source 116, for repeatedmeasurements.

Note that organic coating 109 (corresponding to organic coating 209 inFIG. 2) and organic coating 122 (corresponding to organic coating 222 inFIG. 2) are different. For example, organic coating 109 is optimized forbase sensing (via tunneling current) while organic coating 122 isoptimized for motion control (i.e., preventing thermal motion of the DNA112 in the nanopore 108). In some exemplary embodiments, the organiccoating 109 consists of bifunctional small molecules which at one end(first functionality) form covalent bonds with electrodes (e.g.,conductive layers 102 and 104). At the other end (second functionality)of the organic coating 109 which is exposed in the nanopore 108, theorganic coating 109 consists of functionalities which can form hydrogenbonds with DNA and/or can protonate nucleotides to form acid baseinteractions.

If the (electrodes) conductive layers 102 and 104 are made of metalssuch as gold, palladium, platinum etc., the first functionality whichbonds to conductive layers 102 and 104 can be chosen as thiols,isocyanides, and/or diazonium salts. If the conductive layers 102 and104 are made of titanium nitrides or indium tin oxide (ITO), thecovalent bonding functionality is chosen from phosphonic acid,hydroxamic acid, and/or resorcinol functionality. The small bifunctionalmolecules are designed in such a way that any charge formation due tointeraction with DNA can easily be transferred to the conductive layers102 and 104 and therefore a pi-conjugated moiety (e.g. benzene,diphenyl, etc.) are sandwiched between two functionalities. The secondfunctionality is a group which can form a strong hydrogen bond with DNA.Examples of such groups include but are not limited to alcohols,carboxylic acids, carboxamides, sulfonamides, and/or sulfonic acids.

The organic coating 122 which is designed for motion control, can be thesame as organic coating 109 listed above, but is made on conductivelayer 106 which is much thicker (e.g., two, three, four, five . . .nine, etc., times thicker) than conductive layers 102 and 104, and thisgreater thickness of the conductive layer 106 causes organic coating 122to form more transient bonds with DNA 112 (than organic coating 109 onconductive layers 102 and 104). Further, the organic coating 122 couldalso be derivatized individual nucleic base which can self-assemble ontitanium nitride (TiN) electrodes (such as conductive layer 106).Derivatized individual nucleic bases can form multiple hydrogen bondswith DNA 112, thus providing stronger transient bonding.

FIG. 5 illustrates examples of molecules for the organic coating 109(including organic coating 209) and/or for the organic coating 122(including organic coating 222) according to an exemplary embodiment. InFIG. 5, the example molecules are for self-assembly inside nanopore 108and/or 208 in FIG. 2. As discussed herein, note that the examples forthe organic coating 109 apply to the organic coating 209, and theexamples for the organic coating 122 apply to the organic coating 222.

The organic coating 109 on conductive layers 102 and 104 are designed toform transient bonds 117 to the DNA bases 113 of the DNA molecule 112(and are not able/designed to form transient bonds to the DNA backbone125). The transient bond 117 formed by the organic coating 109 is weakerthan the transient bond 123 formed by the organic coating 122. Forexample, the transient bond 123 is stronger than the transient bond 117in the sense that the transient bond 123 is able to hold the DNAmolecule 112 in place (i.e., in a fixed position) against thermal motion(thermal agitation) of the DNA molecule 112 in the nanopore 108. Thermalmotion causes the DNA molecule 112 to move inside the nanopore 108 evenwhen no voltage is applied by the voltage source 116. The thermal motionis great enough to break the transient bonds 117 formed by the organiccoating 109 on the conductive layers 102 and 104 but is not great enough(i.e., not strong enough) to break the transient bond 123 formed byorganic coating 122 on the conductive layer 106. As such, the transientbond 123 between the conductive layer 106 (via organic coating 122) andthe backbone 125 controls the motion of the DNA molecule 112 inside thenanopore 108. During the moving phase, the voltage is applied by thevoltage source 116 to move (i.e., to break the transient bonds 123 and117) the DNA molecule 112 in the nanopore 108.

Although the transient bond 123 is shown as being connected (bonded) tothe backbone 125, the transient bond 123 produced by the organic coating122 can also bond to the DNA base 113 (via the transient bond 123 aillustrated with dotted line). Also, although not shown for conciseness,the organic coating 122 can be applied to multiple conductive layers(e.g., 2, 3, 4, 5, etc.), and the total transient bonding strength ofthe conductive layers with organic coatings 122 is the sum of theirrespective transient bonds 123. In some embodiments that are not shownin the figure for conciseness, organic coating 122 can also bemade/applied on the surface of the insulating layers 101, 103, 105, 107that are inside of the nanopore 108, to enhance the trapping of DNA 112inside the nanopore 108.

In the following example, when the DNA 112 is driven into the nanopore108 by the voltage source 116, a DNA base 113 a forms a transient bond117 via the organic coating 109 with the (electrode) conductive layer102 and the conductive layer 104. The organic coating 109 applied on theends of the conductive layers 102 and 104 forms a chemical bond (i.e.,transient bond 117) with base 113 a. For explanation purposes and toease understanding, the transient bonds 117 a and 117 b connecting thebase 113 a to conductive layers 102 and 104 (respectively) may be viewedas wires connecting the base 113 a to the conductive layers 102 and 104.When the voltage source 118 is turned on (during the bonded phase),current flows through conductive layer 102, then through organic coating109 a, through the transient bond 117 a, into the base 113 a (whichcauses the tunneling current 120), out through the transient bond 117 b,into the organic coating 109 b, into conductive layer 104, and into theammeter A designated for measuring the tunneling current 120 of the base113 a. When the tunneling current 120 is being measured as discussedabove, the organic coating 122 on the (electrode) conductive layer 106forms the strong transient bond 123 (i.e., chemical bond) to thebackbone 125 and/or the base 113 (by the dotted line for transient bond123 a), in which the transient bond 123 holds the DNA molecule 112 in afixed position against thermal motion that would normally move the DNAmolecule 112 in the nanopore 108. For example, if the transient bond 123were absent, the thermal motion would move the DNA 112 in the nanopore,such that this movement would break the transient bonds 117 a and 117 band prevent the ammeter from measuring the tunneling current 120 of theDNA base 113 a.

The measured tunneling current 120 is a unique current signature of thebase 113 a which is utilized to identify (characterize) the base 113 a(by a software application 605 of a computer 600), as well as subsequentbases 113 having their respective tunneling currents measured. Notethat, the tunneling current 120 between conductive layers 102 and 104does not require any electrical wiring between them as the electronssimply move from one electrode/conductive layer to the other in aquantum mechanical way. There will be a baseline tunneling current whenDNA base 113 a is away (e.g., with distance much longer than thewavelength of an electron) from the two (electrodes) conductive layers102 and 104. When DNA base 113 a is close (e.g., within the distance ofa wavelength of an electron) to the two (electrodes) conductive layers102 and 104, the tunneling path of the electron will be rerouted totunnel from one electrode (e.g., conductive layer 102) to the DNA base113 a and then to the other electrode (e.g., conductive layer 104). Inthis way, the tunneling current (by the electrons) will create asignature (such as an increasing of the baseline tunneling current,typically in the order of tens of pA (picoamperes)) added onto thebaseline tunneling current trace. The tunneling current across DNA basesis dependent on the electronic and chemical structure of the DNA bases,thus each different DNA base will generate a different tunneling currentsignature. The organic coating 122 and 109 form transient bonds 123 and117 respectively with DNA 112, which will help to fix the orientation ofthe DNA base and the relative distance of the DNA base to theelectrodes/conducive layers for improving the resolution of thetunneling current signatures. If organic coating 109 and/or bonding 107is electrically conductive, they will help to shrink the tunneling gapsize and enhance the tunneling current signatures too. If the differencebetween the tunneling current signatures of different DNA bases is smallor stochastic, repeating measurements on the same DNA base can be done,a histogram of the amplitudes of the tunneling current signatures can befit, and the statistical data will provide enough resolution todifferentiate DNA bases 113.

Although the above example explains how the two conductive layers 102and 104 are used to measure the tunneling current 120 for base 113 a inthe nanopore 108, any two layers of conductive layers 102, 104, and 106can be utilized to measure any of the bases 113. For example, when thebase 113 a is driven further through the nanopore 108 (or for adifferent base 113), using voltage source 119 and conductive layers 104and 106, the tunneling current 121 for the base 113 a can be measuredagain with a corresponding ammeter A. Also, with multiple layers ofconductive layers and insulating layers in the membrane 10 and withmultiple voltage sources and ammeters, the tunneling current fordifferent bases 113 can be simultaneously measured in the nanopore 108during the bonded phase as discussed herein.

Now turning to FIG. 2, FIG. 2 illustrates a schematic 200 of anorganic-coated nanopore through a stack of repetitiveinsulating/conducting/insulating/conducting/insulating/ . . . layers forDNA motion control and base sensing, for the case that tunneling currentis measured through a sequence of several DNA bases according to anexemplary embodiment.

In FIG. 2, a membrane 20, which is made of films 201, 202, 203, 204,205, 206, and 207, partitions a reservoir 210 into two parts. Theschematic 200 is a cross-sectional view of the reservoir 210. Ananometer size hole 208 is made through the membrane 20. Membrane parts201, 203, 205, and 207 are electrically insulating while membrane parts202, 204, and 206 are electrically conducting. The films 201 and 207 areelectrical passivation layers, and the films 203 and 205 are insulatinginter-layers between conductive layers. Three conductive layers 202,204, and 206 are shown in the FIG. 2 but exemplary embodiments are notlimited to three conductive layers. It is contemplated that two or moreconductive layers may be utilized. The conductive layers 202, 204, and206 are electrodes and may be considered as electrodes or electrodelayers herein. An organic coating 209 (like the organic coating 109 inFIG. 1) is made on the (inner) surface of conductive layers 202 and 204,and an organic coating 222 (like the organic coating 122 in FIG. 1) ismade on the (inner) surface of the conductive layer 206.

The example implementation in FIG. 2 is almost identical to FIG. 1,except that the transient bonds 217 from adjacent conductive layers arelinked to different DNA bases 213 instead of a single base (like base113 a in FIG. 1) connecting to two conductive layers. Thus, thetunneling currents (signatures) 220 and 221 will be associated with oneor more DNA bases 213. This provides a faster DNA sequencing speed butrequires more resolution on the tunneling signals (such as tunnelingcurrent signature 220) to resolve 4^(n) types of signals (where n is thenumber of bases 213 along the tunneling path, and where 4 is the totalnumber of different DNA bases). One skilled in the art understands thedifferent types of DNA bases.

As discussed above for organic coating 109 and 122, note that organiccoating 209 and 222 are respectively different. For example, organiccoating 209 is optimized for base sensing while organic coating 222 isoptimized for motion control (i.e., preventing thermal motion of the DNA212 in the nanopore 208). FIG. 4 illustrates examples of the moleculesfor the organic coating 222 according to an exemplary embodiment. InFIG. 4, the example molecules of the organic coating 222 are forself-assembly inside the nanopore 208. FIG. 5 illustrates examples ofthe molecules for the organic coating 209 and 222 according to anexemplary embodiment. In FIG. 5, the example molecules of the organiccoating 209 and/or 222 are for self-assembly inside the nanopore 208.

The organic coating 209 on conductive layers 202 and 204 is designed toform transient bonds 217 to the bases 213 of the DNA molecule 112 (andare not able to form transient bonds to the DNA backbone 225). Thetransient bonds 217 formed by the organic coating 209 is weaker than thetransient bond 223 formed by the organic coating 222. For example, thetransient bond 223 is stronger than the transient bond 217 in the sensethat the transient bond 223 is able to hold the DNA molecule 212 inplace (i.e., in a fixed position) against thermal motion (thermalagitation) of the DNA molecule 212 in the nanopore 208. The thermalmotion is great enough to break the transient bonds 217 formed by theorganic coating 209 on the conductive layers 202 and 204 but not strongenough to break the transient bonds 223 formed by organic coating 222 onthe conductive layer 206. Although the transient bond 223 is shown asbeing connected (bonded) to the backbone 225, the transient bond 223produced by the organic coating 222 can also bond to the DNA base 213(as shown by the transient bond 223 a which represented with a dottedline). Also, although not shown for conciseness, the organic coating 222can be applied to multiple conductive layers (e.g., 2, 3, 4, 5, etc.),and the total transient bonding strength of the multiple conductivelayers having organic coatings 222 is the sum of their respectivetransient bonds 223. In some exemplary embodiments that are not shownfor conciseness, the organic coating 222 can also be made on the surfaceof the insulating layers 201, 203, 205, 207 that are inside of thenanopore 208, to enhance the trapping of DNA 212 inside the nanopore208.

An example tunneling path 230 will be discussed when the strongtransient bond 223 via organic coating 222 holds the DNA molecule inplace against thermal motion. The voltage source 216 produces anelectric field to drive the DNA molecule 212 into the nanopore 208. Whenthe voltage source 218 is turned on (during the bonded phase), currentflows through the conductive layer 202, through the organic coating 209a, through the transient bond 217 a, into the DNA base 213 a, throughthe DNA molecule backbone 225 a connecting DNA bases 213 a and 213 b,into the DNA base 213 b, out through the transient bond 217 b, outthrough the organic coating 209 b, into the conductive layer 204, andinto an ammeter A designated to measure tunneling current 220. In thisexample, when the ammeter A measures the tunneling current 220, theammeter actually measures (a combined/composite tunneling current 220contributed to by both the DNA bases 213 a and 213 b) the tunnelingcurrent through a tunneling path 230 combined of the base 213 a and thebase 213 b. As discussed above, the tunneling current 220 (signal)through the tunneling path 230 combined of the base 213 a and the base213 b has to be analyzed in order to indentify individual DNA bases 213a and 213 b. FIG. 6 illustrates a computer 600 having a softwareapplication 605 configured with executable instructions to analyze thetunneling current 220 and thus determine the combination of the base 213a and the base 213 b. There are 4 types of DNA bases and a total of 16types of combinations of the base 213 a and the base 213 b. Differentcombinations of the base 213 a and the base 213 b will generate adifferent tunneling current 220. If the difference between the tunnelingcurrent of different combinations of bases is small or stochastic,repeating measurements on the same combination of DNA bases can be done,a histogram of the amplitudes of the tunneling current signatures can befit, and the statistical data will provide enough resolution to identifythe exact combination of DNA bases. If DNA 212 advances just one baseafter measuring the tunneling current for the combination of the base213 a and base 213 b, the new combination of DNA bases under measurementwill have a difference of only one base from the previous measuredcombination. This will generate redundant/extra data for error checking.

Referring to FIG. 3, a schematic 300 is illustrated of an organic-coatednanochannel with multiple tunneling electrodes for DNA motion controland base sensing according to an exemplary embodiment. FIG. 3illustrates a “lateral nanochannel” version of the implementationsdiscussed for FIGS. 1 and 2. FIG. 3 is a top cross-sectional view of theschematic 300. The nanodevice is FIG. 3 includes a substrate 301 whichmay be made of any insulating and/or semiconductor solid material.

Two reservoirs 302 and 303 are etched into the substrate 301, and alateral nanochannel 304 connects the reservoirs 302 and 303. Reservoir302, reservoir 303, and nanochannel 304 are then filled with ionicsolvent 309. Electrodes 305 a and 305 b (generally referred to aselectrodes 305) are a pair of electrodes with a nanometer size gapbetween them, and the end of each electrode 305 a and 305 b isintegrated within the nanochannel 304 while the other end is in thesubstrate 301. Electrodes 306 a and 306 b (generally referred to aselectrodes 306) are another pair of electrodes with a nanometer size gapbetween them, and the end of each electrode 306 a and 306 b isintegrated within the nanochannel 304 while the other end is in thesubstrate 301. Although only two pairs of electrodes (electrodes 305 and306) are shown in FIG. 3, it is contemplated that electrodes of one ormore pairs (e.g., 3, 4, 5, 6, 7, and/or 10 pairs of electrodes) may beutilized as discussed herein.

Organic coating 307 a and 307 b (generally referred to as organiccoating 307) are made on the exposed surface of electrodes 305 a and 305b in the nanochannel 304, and organic coating 308 a and 308 b (generallyreferred to as organic coating 308) are made on the exposed surface ofelectrodes 306 a and 306 b. The organic coating 307 can be any organiccoating that has a transient bond 315, such as a hydrogen bond, withindividual DNA bases 311 (DNA 310 illustrates the whole DNA molecule).The organic coating 308 can be any organic coating that has a transientbond 335, such as a hydrogen bond, to individual DNA bases 311 and/orDNA backbones 325 of the whole DNA molecule 310. The minimum number ofpairs of electrodes is determined by the need (of the user) for trappingDNA molecules 310 inside the nanochannel 304 (i.e., similar to thenanopores 108 and 208) against thermal agitation via these transientbonds 315 and 335. DNA molecules 310 were loaded into the nanochannel304 by an electrical voltage bias of voltage source 312 (producing anelectric field) applied across the nanochannel 304 via twoelectrochemical electrodes 313 and 314, which were dipped in the solvent309 of the two reservoirs 302 and 303.

With enough pairs of electrodes (e.g., two), thus enough transient bonds315 and/or 335, the DNA molecule 310 can be trapped inside thenanochannel 304 against thermal motion (e.g., when the voltage ofvoltage source 312 is not applied). With a predefined voltage applied byvoltage source 312, these transient bonds 315 and 335 can be broken, andthe DNA molecule 310 can be driven through the nanochannel 304 via theelectrical field. If the voltage source 312 is pulsed, the DNA molecule310 will experience a bonded phase and a moving phase (as discussedabove). During the bonded phase, voltages sources 316 and 317 can beapplied on electrode pair 305 and 306 respectively. Tunneling currents318 and 319 can be measured with ammeters A respectively correspondingto each tunneling current 318 and 319. Since the DNA base 311 is in afixed bonded position by the transient bonds 315 and 335, these measuredtunneling current (signatures) 318 and 319 can be used to identifyindividual DNA bases 311 by the software application 605 of the computer600, e.g., by a user utilizing the computer 600 (to view the tunnelingcurrent signatures 318 and 319), and/or by a user viewing thecorresponding ammeters A. The moving phase will advance the DNA molecule310 for identifying other DNA bases 311. The DNA 310 can also be drivenback and forth through the nanochannel 304 many times by switching thepolarity of the external voltage bias of the voltage source 312, forrepeated measurements.

Note that the organic coating 307 and 308 are different. Organic coating307 (the same as organic coatings 109 and 209) is optimized for base 311sensing while organic coating 308 (the same as organic coating 122 and222) is optimized for motion control (i.e., stopping the thermal motionfrom moving the DNA molecule 310). In one exemplary embodiment,electrode (metal) 305 may be TiN, and electrode 306 may be gold (Au),platinum, and/or silver. The organic coating 307 which is designed forbase sensing could be a derivatized individual nucleic base which canself-assemble on TiN electrodes 305. For example, these organic coatings307 could be formed by individual bases which have either phophonic acidand/or hydroxamic acid functionality. Since each base 311 has adifferent hydrogen bonding than the other three bases, these coatingscan be used to sense the individual bases 311. FIG. 4 illustratesexamples of the molecules for the organic coating 308 (including organiccoatings 122 and 222) according to an exemplary embodiment. In FIG. 4,the example molecules of the organic coating 308 are for self-assemblyon the electrodes 305 inside the nanochannel 304. FIG. 5 illustratesexamples of the molecules for the organic coating 307 and 308 accordingto an exemplary embodiment. In FIG. 5, the example molecules of theorganic coating 307 and/or 308 are for self-assembly on the electrodes305 inside the nanochannel 304.

An example of measuring the tunneling current 318 is provided below forthe left circuit while the strong transient bonds 335 a and 335 b (inthe right circuit) hold the DNA molecule 310 in place for measurementagainst thermal motion (which would normally cause the DNA molecule 310to move in the nanochannel 304). When the voltage source 318 is turnedon during the bonded phase, electrical current flows through electrode305 b, through organic coating 307 b, through the transient bond 315 b,into base 311 a (which produces the tunneling current 318), out throughthe transient bond 315 a, out through organic coating 307 a, throughelectrode 305 a, and into the corresponding ammeter A to measure thetunneling current 318. In exemplary embodiments, numerous circuits(e.g., 2, 3, 4, 5, and/or 10) as shown in FIG. 3 can simultaneouslymeasure the tunneling currents for numerous bases 311 of the DNAmolecule 310. Each circuit would have its corresponding voltage source(like voltage source 316) and its ammeter A for measuring the tunnelingcurrent of its particular base 311 as discussed herein.

The electrodes 305 a and 305 b (similarly electrodes 306 a and 306 b)are two separate electrodes on opposite sides of the nanochannel 304connected by a wire at the ends not in the nanochannel 304. The ends ofelectrodes 305 a and 305 b (similarly electrodes 306 a and 306 b) in thenanochannel 304 which have organic coating 307 a and 307 b (similarlyorganic coatings 308 a and 308 b) do not touch and are not connected bya wire. Instead, the transient bonds 315 a and 315 b (similarlytransient bonds 335 a and 335 b) operatively connect/couple theelectrodes 305 a and 305 b (electrodes 306 a and 306 b) together throughthe base 311 a via the organic coating 307 a and 307 b.

The organic coating 307 on electrodes 305 a and 305 b is designed toform transient bonds 315 a and 315 b to the bases 313 of the DNAmolecule 112 (and are not able to form transient bonds to the backbone325). The transient bonds 315 a and 315 b formed by the organic coating307 are weaker than the transient bond 335 formed by the organic coating308. For example, the transient bond 335 is stronger than the transientbond 315 in the sense that the transient bond 335 is able to hold theDNA molecule 310 in place (i.e., in a fixed position) against thermalmotion (thermal agitation) of the DNA molecule 310 in the nanochannel304. The thermal motion is great enough to break the transient bonds 315formed by the organic coating 307 on the electrodes 305 a and 305 b butnot strong enough to break the transient bonds 335 formed by organiccoating 308 on the electrodes 306 a and 306 b. Although the transientbond 335 is shown as being connected (bonded) to the base 311, thetransient bond 335 produced by the organic coating 308 can also bond tothe DNA backbone 325. Also, although not shown for conciseness, theorganic coating 308 can be applied to multiple electrode pairs (e.g., 2,3, 4, 5, etc.), and the total transient bonding strength of the multipleelectrode pairs having organic coatings 308 is the sum of theirrespective transient bonds 335.

Further, in one implementation of an exemplary embodiment,electrodes/conductive layers 106, 206, and 306 have more contact areawith their respective organic coatings 122, 222, and 308 in theirrespective nanopores/nanochanels 108, 208, and 304 than theelectrodes/conductive layers 102, 104, 202, 204, and 305 with theirrespective organic coatings 109, 209, and 307.

FIG. 7 illustrates a method 700 for DNA sequencing a nanodeviceaccording to an exemplary embodiment, and reference can be made to FIGS.1 and 2.

At block 705, a nanopore 108, 208 is formed through multiple addressableconductive layers, which are separated by insulating layers. Theaddressable conductive layers 102, 104, 106, 202, 204, 206 can beaddressed (i.e., have voltage individually applied as desired) byrespective voltage sources 118, 119, 218, 219.

At block 710, different organic coatings (such as organic coatings 109,122, 209, 222) are provided on different conductive layers at the innersurface of the nanopore. Some organic coatings have stronger transientbonds to bases and/or backbones of the DNA molecules 112, 212.

At block 715, the transient bonding between the organic coating andindividual DNA bases and/or backbones is leveraged to control the motionof the DNA as well as to fix (hold) the DNA base for characterization.Characterization is measuring the tunneling currents 120, 121, 220, 221as discussed herein through the conductive layers (electrodes), organiccoatings, and transient bonds. Characterization (i.e., distinguishingthe tunneling current signature of a base) can be performed by thecomputer 600.

At block 720, DNA bases are differentiated by using the tunnelingcurrent from one conductive layer to the transient bond, the DNA base,the other transient bond, and finally to another conductive layer.Differentiation of the DNA base (e.g., base 113 or 213) can be bycausing the tunneling current (e.g., tunneling current 120) to bedisplayed (in a graph/plot of, e.g., magnitude versus time/frequency) onthe display 45 of the computer 600. The computer 600 may comprise and/orbe coupled to an ammeter A so that the tunneling current signature forone base 113, 213 is viewed, measured, recorded, and/or analyzed by thesoftware application 605 (and/or a user), and the software application605 (or user viewing the graph/plot) can differentiate one base 113, 213from a different base 113, 213 of the DNA molecule 112, 212, based ontheir respective tunneling currents because the tunneling current is asignature of each particular base 113.

Also, as discussed above, a first tunneling current in base 213 a can becombined with a second tunneling current in base 213 b to be measured asthe combined tunneling current 220 by the corresponding ammeter A. Thecomputer 600 via software application 605 can measure, differentiate,record, display (as two graphs/plots (and/or a single graph/plot) on thedisplay 45), and/or analyze the first and second tunneling currentsforming the tunneling current 220. The computer 600 can resolve thefirst and second tunneling currents from the combined tunneling current220.

At block 725, some organic coatings 109, 209 are optimized for basesensing while the other organic coatings 122, 222 are optimized formotion control (i.e., holding the DNA molecule 112, 212 in place formeasurements). One conductive layer 106 coated with organic coating 109forms a (single) stronger transient bond 123 than multiple conductivelayers 102 and 104 (and more) with organic coating 209 forming multipletransient bonds 117. Likewise, a single transient bond 223 via organiccoating 222 is stronger than multiple transient bonds 217 via organiccoating 209.

FIG. 8 illustrates a method 800 for sequencing DNA molecules in ananodevice according to an exemplary embodiment, and reference can bemade to FIG. 3.

At block 805, multiple pairs of electrodes 305 and 306 each with ananometer size gap there between can be formed along the nanochannel304. Different organic coatings 307 and 308 can be applied on differentelectrodes 305 and 306 at the inner surface of the nanochannel 304, atblock 810.

At block 815, the transient bondings 315 and 335 are formed between theorganic coating 307 and 308 and individual DNA bases 311 (and/orbackbone 325) to control the motion of DNA molecule 310 as well as tofix the DNA base 311 for characterization. Characterization is measuringthe tunneling currents 318 and 319 as discussed herein through theelectrodes, organic coatings, and transient bonds to recognize/displaythe individual tunneling currents (signatures) for DNA bases 311.

At block 820, each DNA base such as base 311 a is differentiated usingthe tunneling current (e.g., tunneling current 318) between the pair ofelectrodes 305 through its bonded DNA base 311 a. Differentiation can beperformed by computer 600 (and/or a user utilizing the computer 600) asdiscussed herein.

At block 825, some organic coatings 307 are optimized for base 311sensing (characterization) while the other organic coatings 308 areoptimized for motion control (i.e., stopping the DNA molecule 310against thermal motion/agitation).

Now turning to FIG. 6, FIG. 6 illustrates a block diagram of thecomputer 600 having various software and hardware elements forimplementing exemplary embodiments.

The diagram depicts the computer 600 which may be any type of computingdevice and/or test equipment (including ammeters). The computer 600 mayinclude and/or be coupled to memory 15, a communication interface 40,display 45, user interfaces 50, processors 60, and software 605. Thecommunication interface 40 comprises hardware and software forcommunicating over a network and connecting (via cables, plugs, wires,electrodes, etc.) to the nanodevices discussed herein. Also, thecommunication interface 40 comprises hardware and software forcommunicating with, operatively connecting to, reading, and controllingvoltage sources, ammeters, tunneling currents, etc., as discussedherein. The user interfaces 50 may include, e.g., a track ball, mouse,pointing device, keyboard, touch screen, etc, for interacting with thecomputer 600, such as inputting information, making selections,independently controlling different voltages sources, and/or displaying,viewing and recording tunneling current signatures for each base, etc.

The computer 600 includes memory 15 which may be a computer readablestorage medium. One or more applications such as the softwareapplication 605 (e.g., a software tool) may reside on or be coupled tothe memory 15, and the software application 605 comprises logic andsoftware components to operate and function in accordance with exemplaryembodiments in the form of computer executable instructions. Thesoftware application 605 may include a graphical user interface (GUI)which the user can view and interact with according to exemplaryembodiments.

As will be appreciated by one skilled in the art, aspects of the presentinvention may be embodied as a system, method or computer programproduct. Accordingly, aspects of the present invention may take the formof an entirely hardware embodiment, an entirely software embodiment(including firmware, resident software, micro-code, etc.) or anembodiment combining software and hardware aspects that may allgenerally be referred to herein as a “circuit,” “module” or “system.”Furthermore, aspects of the present invention may take the form of acomputer program product embodied in one or more computer readablemedium(s) having computer readable program code embodied thereon.

Any combination of one or more computer readable medium(s) may beutilized. The computer readable medium may be a computer readable signalmedium or a computer readable storage medium. A computer readablestorage medium may be, for example, but not limited to, an electronic,magnetic, optical, electromagnetic, infrared, or semiconductor system,apparatus, or device, or any suitable combination of the foregoing. Morespecific examples (a non-exhaustive list) of the computer readablestorage medium would include the following: an electrical connectionhaving one or more wires, a portable computer diskette, a hard disk, arandom access memory (RAM), a read-only memory (ROM), an erasableprogrammable read-only memory (EPROM or Flash memory), an optical fiber,a portable compact disc read-only memory (CD-ROM), an optical storagedevice, a magnetic storage device, or any suitable combination of theforegoing. In the context of this document, a computer readable storagemedium may be any tangible medium that can contain, or store a programfor use by or in connection with an instruction execution system,apparatus, or device.

A computer readable signal medium may include a propagated data signalwith computer readable program code embodied therein, for example, inbaseband or as part of a carrier wave. Such a propagated signal may takeany of a variety of forms, including, but not limited to,electro-magnetic, optical, or any suitable combination thereof. Acomputer readable signal medium may be any computer readable medium thatis not a computer readable storage medium and that can communicate,propagate, or transport a program for use by or in connection with aninstruction execution system, apparatus, or device.

Program code embodied on a computer readable medium may be transmittedusing any appropriate medium, including but not limited to wireless,wireline, optical fiber cable, RF, etc., or any suitable combination ofthe foregoing.

Computer program code for carrying out operations for aspects of thepresent invention may be written in any combination of one or moreprogramming languages, including an object oriented programming languagesuch as Java, Smalltalk, C++ or the like and conventional proceduralprogramming languages, such as the “C” programming language or similarprogramming languages. The program code may execute entirely on theuser's computer, partly on the user's computer, as a stand-alonesoftware package, partly on the user's computer and partly on a remotecomputer or entirely on the remote computer or server. In the latterscenario, the remote computer may be connected to the user's computerthrough any type of network, including a local area network (LAN) or awide area network (WAN), or the connection may be made to an externalcomputer (for example, through the Internet using an Internet ServiceProvider).

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer program instructions. These computer program instructions maybe provided to a processor of a general purpose computer, specialpurpose computer, or other programmable data processing apparatus toproduce a machine, such that the instructions, which execute via theprocessor of the computer or other programmable data processingapparatus, create means for implementing the functions/acts specified inthe flowchart and/or block diagram block or blocks.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or blockdiagram block or blocks.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof code, which comprises one or more executable instructions forimplementing the specified logical function(s). It should also be notedthat, in some alternative implementations, the functions noted in theblock may occur out of the order noted in the figures. For example, twoblocks shown in succession may, in fact, be executed substantiallyconcurrently, or the blocks may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each block of the block diagrams and/or flowchart illustration, andcombinations of blocks in the block diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneore more other features, integers, steps, operations, elementcomponents, and/or groups thereof.

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present invention has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Theembodiment was chosen and described in order to best explain theprinciples of the invention and the practical application, and to enableothers of ordinary skill in the art to understand the invention forvarious embodiments with various modifications as are suited to theparticular use contemplated

The flow diagrams depicted herein are just one example. There may bemany variations to this diagram or the steps (or operations) describedtherein without departing from the spirit of the invention. Forinstance, the steps may be performed in a differing order or steps maybe added, deleted or modified. All of these variations are considered apart of the claimed invention.

While the exemplary embodiments of the invention have been described, itwill be understood that those skilled in the art, both now and in thefuture, may make various improvements and enhancements which fall withinthe scope of the claims which follow. These claims should be construedto maintain the proper protection for the invention first described.

What is claimed is:
 1. A nanodevice, comprising: a reservoir filled witha conductive fluid; a membrane separating the reservoir, the membranecomprising electrode layers separated by insulating layers; and ananopore formed through the membrane, a certain electrode layer having afirst type of organic coating and a pair of electrode layers having asecond type of organic coating inside the nanopore; wherein the firsttype of organic coating on the certain electrode layer forms a motioncontrol transient bond to a molecule in the nanopore for motion controlof the molecule; wherein the second type of organic coating on the pairof electrode layers forms a first transient bond to a first base and asecond transient bond to a second base of the molecule in the nanopore;wherein the first type of organic coating is selected from the groupconsisting of hydroxamic acid and resorcinol and the second type oforganic coating is different from the first type of organic coating;wherein, when a voltage is applied to the pair of electrode layers atunneling current is generated though the first base along the moleculeto the second base in the nanopore, the tunneling current traveling viathe first and the second transient bonds respectively to be measured asa current signature for distinguishing the first base and the secondbase; and wherein the motion control transient bond is stronger than thefirst and the second transient bonds.
 2. The nanodevice of claim 1,wherein the motion control transient bond has strength to hold themolecule in the nanopore against thermal motion.
 3. The nanodevice ofclaim 1, wherein the first type of organic coating on the certainelectrode layer covers greater surface area on the certain electrodelayer than the second type of organic coating on the pair of electrodelayers.
 4. The nanodevice of claim 1, wherein the certain electrodelayer is thicker than each of the pair of electrode layers.
 5. Thenanodevice of claim 1, wherein the reservoir is split into first andsecond reservoir parts.
 6. The nanodevice of claim 5, wherein first andsecond electrodes are in the first and second reservoir partsrespectively.
 7. The nanodevice of claim 6, wherein the first and secondelectrodes are electrochemical electrodes.
 8. The nanodevice of claim 1,wherein the first and second electrodes are configured to receive anexternal voltage such that the motion control transient bond, the firsttransient bond, and the second transient bond are broken to move themolecule in the nanopore.
 9. The nanodevice of claim 1, wherein thesecond type of organic coating is selected from the group consisting ofalcohols carboxylic acids, carboxamides, sulfonamides, and sulfonicacids.
 10. The nanodevice of claim 1, wherein material of the pair ofelectrodes is selected from the group consisting of gold, palladium, andplatinum.
 11. The nanodevice of claim 1, wherein material of the pair ofelectrodes is selected from the group consisting of titanium nitrides orindium tin oxide.
 12. The nanodevice of claim 1, further comprisingother electrode layers having the first type of organic coating.
 13. Thenanodevice of claim 12, wherein the other electrode layers are inaddition to the certain electrode layer.
 14. The nanodevice of claim 13,wherein the other electrode layers are conductive layers.
 15. Thenanodevice of claim 13, wherein a total of the certain electrode layerand the other electrode layers is
 3. 16. The nanodevice of claim 13,wherein a total of the certain electrode layer and the other electrodelayers is
 4. 17. The nanodevice of claim 13, wherein a total of thecertain electrode layer and the other electrode layers is
 5. 18. Thenanodevice of claim 1, wherein one or more of the insulating layersincludes the first type of organic coating.
 19. The nanodevice of claim1, wherein the insulating layers include the first type of organiccoating.